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甘露糖化硫酸巴龙霉素载固体脂质纳米粒治疗急性弓形虫病的评价。

Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis.

机构信息

Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Regulatory Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Front Cell Infect Microbiol. 2020 Feb 13;10:33. doi: 10.3389/fcimb.2020.00033. eCollection 2020.

DOI:10.3389/fcimb.2020.00033
PMID:32117807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7031658/
Abstract

is a zoonotic intracellular protozoan with worldwide distribution. Acute and severe toxoplasmosis are commonly reported in patients who suffer from acquired/congenital immune deficiency. This study aimed to synthesize mannosylated paromomycin-loaded solid lipid nanoparticles (PM-SLN-M) and to evaluate them on acute toxoplasmosis. SLN was synthesized and then loaded by 7 mg/mL paromomycin sodium. Mannose coating was performed, and after washing, the size, zeta potential, and loading percentage were calculated. To evaluate the cell toxicity, an MTT assay was performed on Vero cells by different concentrations (log 10) of SLN, PM-SLN-M, and PM-SLN. In addition, the anti- effects were also evaluated using trypan-blue staining and scanning electron microscopy (SEM). An MTT assay was also employed to evaluate the effects of PM and PM-SLN-M on intracellular . A 6-month stability test of PM-SLN and PM-SLN-M represented that the characteristics all remained constant. The cell viability assay demonstrated that PM-SLN-M had lower cell toxicity (<20%) compared to PM-SLN (<30%) and PM (<40%). Statistical analysis showed that PM-SLN-M significantly killed ~97.555 ± 0.629 (95% CI: 91.901 to 103.209; < 0.05) of tachyzoites. More than 50% of infected Vero cells remained viable in concentrations more than 0.07 μg/mL and 7 μg/mL of PM and PM-SLN-M, respectively. SEM analysis showed that tachyzoites were changed in both size and morphology facing with PM-SLN-M. Our findings indicated that synthesized PM-SLN-M had anti- activity without significant host cell toxicity at the highest concentration. Our study demonstrated that PM was able to kill intracellular in lower concentration in comparison to PM-SLN-M, although PM-SLN-M showed lower cytotoxic effects on Vero cells.

摘要

刚地弓形虫是一种具有全球分布的、嗜细胞内的原虫,其急性和重症感染通常发生于获得性/先天性免疫缺陷患者中。本研究旨在合成甘露糖修饰的硫酸巴龙霉素载药固体脂质纳米粒(PM-SLN-M),并对其急性弓形虫病治疗效果进行评价。通过 7mg/mL 硫酸巴龙霉素钠溶液负载 SLN 后,进行甘露糖包被,经过洗涤后,计算其粒径、Zeta 电位和载药量。通过不同浓度(log 10)的 SLN、PM-SLN-M 和 PM-SLN 对 Vero 细胞进行 MTT 实验,评价细胞毒性。同时,通过台盼蓝染色和扫描电子显微镜(SEM)观察评价抗弓形虫效果。另外,还通过 MTT 实验评价 PM 和 PM-SLN-M 对细胞内弓形虫的作用。PM-SLN 和 PM-SLN-M 的 6 个月稳定性测试表明,其特征均保持不变。细胞活力测定结果表明,PM-SLN-M 的细胞毒性低于 PM-SLN(<30%)和 PM(<40%)(<20%)。统计学分析表明,PM-SLN-M 能显著杀灭97.555±0.629(95%CI:91.901103.209; <0.05)的速殖子。在浓度高于 0.07μg/mL 和 7μg/mL 的 PM 和 PM-SLN-M 中,超过 50%的感染 Vero 细胞仍然存活。SEM 分析显示,PM-SLN-M 能改变弓形虫的大小和形态。我们的研究结果表明,在最高浓度下,合成的 PM-SLN-M 具有抗弓形虫活性,而宿主细胞毒性不明显。与 PM-SLN-M 相比,PM 能在较低浓度下杀死细胞内的弓形虫,尽管 PM-SLN-M 对 Vero 细胞的细胞毒性较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/46eb9898e6c7/fcimb-10-00033-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/44dcd023f73c/fcimb-10-00033-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/a61059788812/fcimb-10-00033-g0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/ac993ff2daa7/fcimb-10-00033-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/aac2a90f3615/fcimb-10-00033-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/46eb9898e6c7/fcimb-10-00033-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/44dcd023f73c/fcimb-10-00033-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/3b91e1c103b1/fcimb-10-00033-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/a61059788812/fcimb-10-00033-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/bd4958cf1562/fcimb-10-00033-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/ac993ff2daa7/fcimb-10-00033-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/aac2a90f3615/fcimb-10-00033-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7e/7031658/46eb9898e6c7/fcimb-10-00033-g0007.jpg

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